Primecuts – This Week In The Journals

February 24, 2014

By Miguel A. Saldivar, MD

Peer Reviewed

This week’s edition of Primecuts brings highlights from studies on a variety of topics ranging from prescription drug abuse to cost-effective medical care. Given that the CDC classified the issue of prescription drug abuse/overdose as an “epidemic” [1,2,3] in 2012, we begin with a paper on opiate prescriptions in the Medicare population.

The relationship between use of multiple opiate providers and hospitalizations

The British Medical Journal published a retrospective observational study [4] that analyzed data on opiate prescriptions in 2010 from a random sample of Medicare beneficiaries with Part D prescription drug coverage. Opiates were defined using the National Drug Code’s criteria and excluded those used as antidiarrheals and antitussives. The study focused on beneficiaries filling opioid prescriptions from multiple providers, the proportion of prescriptions concurrently supplied, and hospital admissions related to use of opiates from multiple prescribers.

Of all beneficiaries that filled opioid prescriptions (n=1,808,355), 66.8% filled two or more prescriptions (n=1,208,100). Of these, 60.7% of patients had prescriptions from two or more providers. Importantly, a total of 143,344 (11.9%) beneficiaries utilized 4 or more prescribers, and in the majority of these cases (77.2%) the patient’s “dominant provider” prescribed less than half of the opiates received. Researchers also noted a direct correlation between opiate-related hospital admissions and the number of opiate prescribers: 1.63% (95% CI, 1.58%-1.67%) for one prescriber, 2.08% (95% CI, 2.03%-2.14%) for two prescribers, 2.87% (95% CI, 2.77%-2.97%) for three prescribers, and 4.83% (95% CI, 4.70%-4.96%) for four or more prescribers (p<0.01).

This study suggests a correlation between the utilization of multiple opiate prescribers and an increased risk for hospitalization. It also continues to raise concerns over the misuse of prescription opiates, the fragmentation of individual medical care, and the phenomenon of patients “doctor shopping” for medications.

Treatment Protocols for Acetaminophen Overdose

Continuing with the theme of toxicology, The Lancet published a double-blind, randomized factorial study comparing two dosage protocols for use of intravenous acetylcysteine to treat acetaminophen overdose [5]. This study compared the standard UK treatment schedule (weight based, lasting 20-25 hours) to a shorter modified weight-based, 12-hour protocol. The addition of ondansetron to these regimens was also compared, as nausea and vomiting are common side effects of acetylcysteine administration. Patients presenting within 8 hours of acetaminophen ingestion with serum levels greater than 200mg/L (or 100mg/L at 4 hours) were randomized to either (1) Ondansetron plus 12-hour acetylcysteine regimen, (2) Ondansetron plus standard acetylcysteine schedule, (3) Placebo plus 12-hour acetylcysteine regimen or (4) Placebo plus standard acetylcysteine schedule.

The primary outcome was the proportion of patients who did not vomit, retch, or require rescue antiemetics (IV cyclizine) within 2 hours of acetylcysteine initiation. Thirty six percent of patients assigned to the shorter protocol experienced emesis or retching, compared to 65% in the standard protocol (regardless of allocation to ondansetron or placebo). Furthermore, 41% of patients receiving ondansetron experienced emesis/retching compared to 61% in the placebo group (regardless of acetylcysteine protocol allocation).

The study suggests that the 12-hour modified protocol is better tolerated (less vomiting/retching) than the current UK standards. However, further study is needed to determine how much of a role ondansetron played in preventing the vomiting and retching that was being analyzed as the primary outcome.

The use of Citalopram in Alzheimer’s-related agitation

Moving on to news in Geriatrics, the Journal of the American Medical Association (JAMA) published a randomized, placebo-controlled, double-blind study evaluating the efficacy of citalopram for agitation in Alzheimer’s disease. Patients with probable Alzheimer’s Disease (n=186) were randomized to receive either citalopram (n=94) or placebo (n=92) for 9 weeks. Citalopram was started at 10mg/day and titrated to 30mg/day over 3 weeks. Primary outcome measures were scores from two standardized agitation scales measured at baseline and again at 9 weeks. Participants included in the study lived at home with caregiver support. Those with concomitant depression, psychosis, or prolonged QTc were excluded. Results indicated that 40% of citalopram patients showed moderate-to-marked improvement in symptoms of agitation vs 26% in the placebo group (NNT = 7). However, patients receiving citalopram had greater cognitive decline on the Mini-Mental Status Exam by an average of -1.05 points (95% CI, -1.97 to -0.13, p=0.03) as compared to patients receiving placebo. The citalopram group also had a greater increase in QTc interval (mean 18.1 ms; 95% CI, 6.1-30.1, p=0.004), in addition to a substantial number of adverse events, including anorexia, diarrhea, and falls.

Although symptoms of agitation improved with citalopram use, its effects on cognitive decline and QTc prolongation remain concerning in this population already at risk for multiple comorbidities. As with several other medications, use should be judicious with consideration of individual circumstances.

Recommendations to reduce health care costs in the Emergency Department

Also published in JAMA is a study aimed at identifying a “top 5 list” of procedures in the Emergency Room that are considered low value and perhaps avoidable as part of cost-saving efforts [7]. The study follows on the footsteps of the “Choosing Wisely Campaign” launched by the American Board of Internal Medicine as a potential strategy to reduce the overuse of services that provide low clinical yield. This study gathered a Technical Expert Panel (TEP) from within an integrated healthcare system in Eastern Massachusetts that includes two academic and four community-hospital Emergency Departments. The TEP identified 64 unique emergency room tests, treatments, and procedures and then ranked them on the basis of contribution to cost, benefit to patients and actionability by an EM practitioner. Two hundred and eighty three clinicians were then surveyed to rank these items according to their potential for cost-reduction. The TEP then selected a list of 5 items and made the following recommendations to decrease costs for low-utility tests/procedures: (1) Do not use CT of the cervical spine for trauma patients that do not meet the National Emergency X-Radiography Utilization Study (NEXUS) criteria or the Canadian C-spine rule. (2) Do not order CT PE protocol until the patient is first risk-stratified. (3) Do not order MRI of lumbar spine for low back pain without high-risk features. (4) Do not order head CTs for mild traumatic head injury unless patients meet the New Orleans Criteria or the Canadian CT Head Rule. (5) Avoid ordering coagulation studies for patients without hemorrhage or suspected coagulopathy.

Although Emergency medicine clinicians created this list, several of the recommendations are applicable to Medicine practice as well. The study is limited in that it is focused on a single health care system and the research team did not use formal cost data. Despite this, their recommendations are logical, sensible and contribute to the ongoing conversation of clinicians’ responsibility to the patient while being mindful of the rising costs of healthcare.


The Journal of Nature Medicine presents an article on the search for new therapies for marijuana intoxication [8]. This is timely given critic’s concern that increasing relaxation on marijuana laws in certain states could lead to an increase in substance abuse and related complications.

The New England Journal of Medicine published a review article on Lung Auscultation [9], including detailed descriptions of potential physical exam findings and their clinical relevance.

– The Annals of Internal Medicine publicized the US Preventive Services Task Force’s recommendation statement on risk assessment, genetic counseling and testing for BRCA-related cancers in women [10].

– The Journal of Toxicological Sciences presents a study on the AroER Tri-screen, a novel assay to detect Endocrine-Disrupting Chemicals (EDCs) that are estrogenic, anti-estrogenic, and/or aromatase-like. The assay can potentially be used to screen for substances that may present a health hazard (e.g estrogen agonists in patients with ER positive breast cancer) and those that may aid existing treatments (e.g., estrogen antagonists in patients with ER positive breast cancer). [11].

Dr. Miguel A. Saldivar is a 1st year resident at NYU Langone Medical Center

Peer Reviewed by Jessica Taff, MD, Contributing Editor, NYU Langone Medical Center

Image courtesy of Wikimedia Comons


1. Paulozzi L, Baldwin G, Franklin G, et al. CDC Grand Rounds: Prescription Drug Overdoses — a U.S. Epidemic. Morbidity and Mortality Weekly Report. January 13, 2012 / 61(01);10-13.

2. Office of National Drug Control Policy. Prescription Drug Abuse.

3. Kirschner N, Ginsburg J, Snyder Sulmasy L, for the Health and Public Policy Committee of the American College of Physicians. Prescription Drug Abuse: Executive Summary of a Policy Position Paper From the American College of Physicians. Ann Intern Med. 2014;160(3):198-200-200. doi:10.7326/M13-2209.

4. Jena AB, Goldman D, Weaver L, et al. Opioid prescribing by multiple providers in Medicare: retrospective observational study of insurance claims. BMJ 2014;348:g1393.

5. Bateman DN, Dear JW, Thanacoody, HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. The Lancet, Volume 383, Issue 9918, Pages 697 – 704, 22 February 2014. doi:10.1016/S0140-6736(13)62062-0.

6. Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of Citalopram on Agitation in Alzheimer Disease; The CitAD Randomized Clinical Trial. JAMA. 2014;311(7):682-691. doi:10.1001/jama.2014.93.

7. Schuur JD, Carney DP, Lyn ET, et al. A Top-Five List for Emergency Medicine. A Pilot Project to Improve the Value of Emergency Care. JAMA Intern Med. Published online February 17, 2014. doi:10.1001/jamainternmed.2013.12688.

8. Owens B. With pot now legal, therapies sought to blunt high of marijuana. Nature Medicine 20, 107 (2014); doi:10.1038/nm0214-107.

9. Bohadana A, Izbicki G, Kraman SS. Fundamentals of Lung Auscultation. N Engl J Med 2014; 370:744-751; February 20, 2014; DOI: 10.1056/NEJMra1302901.

10. Moyer, VA. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2014;160(4):271-281-281. doi:10.7326/M13-2747.

11. Chen S, Zhou D, Hsin LY, et al. AroER Tri-Screen™ is a Biologically Relevant Assay for Endocrine Disrupting Chemicals Modulating the Activity of Aromatase and/or the Estrogen Receptor. Toxicol Sci. 2014 Feb 5.